Liu Xiaoli, Yang Peizeng, Lin Xiaomin, Ren Xiangrong, Zhou Hongyan, Huang Xiangkun, Chi Wei, Kijlstra Aize, Chen Ling
Uveitis Study Center, Zhongshan Ophthalmic Center, Sun Yat-sen University, State Key Laboratory of Ophthalmology, International Uveitis Study Laboratory of Guangdong Province, Guangzhou, P.R. China.
Clin Immunol. 2009 May;131(2):333-42. doi: 10.1016/j.clim.2008.12.007. Epub 2009 Feb 5.
Cyclosporin A (CsA) and corticosteroids are extensively used in the treatment of autoimmune diseases including Vogt-Koyanagi-Harada (VKH) syndrome. The exact immunosuppressive mechanisms of these drugs are not exactly known. Th1 and Th17 cells are important populations involved in autoimmune diseases. In this study, we investigated whether they are involved in VKH syndrome and how their function is affected by CsA and corticosteroids. The results showed that IL-17, IFN-gamma, RORgammat and T-bet were upregulated in patients with active uveitis. CsA and corticosteroids were able to downregulate all these elevated levels which correlated with the clinical improvement of the uveitis. In vitro experiments showed that CsA and dexamethasone could decrease the frequencies of Th1 and Th17 cells and inhibit IL-17 and IFN-gamma production. These data suggest that an upregulated Th1 and Th17 response is associated with active VKH syndrome. CsA and corticosteroids may exert their immunosuppressive role by downregulating Th1 and Th17 cells.
环孢素A（CsA）和皮质类固醇被广泛用于治疗包括Vogt-小柳原田（VKH）综合征在内的自身免疫性疾病。这些药物确切的免疫抑制机制尚不完全清楚。Th1细胞和Th17细胞是参与自身免疫性疾病的重要细胞群体。在本研究中，我们调查了它们是否参与VKH综合征以及它们的功能如何受到CsA和皮质类固醇的影响。结果显示，活动性葡萄膜炎患者的白细胞介素-17（IL-17）、γ-干扰素（IFN-γ）、维甲酸相关孤核受体γt（RORgammat）和T-盒转录因子（T-bet）表达上调。CsA和皮质类固醇能够下调所有这些升高的水平，这与葡萄膜炎的临床改善相关。体外实验表明，CsA和地塞米松可降低Th1细胞和Th17细胞的频率，并抑制IL-17和IFN-γ的产生。这些数据表明，Th1和Th17反应上调与活动性VKH综合征相关。CsA和皮质类固醇可能通过下调Th1细胞和Th17细胞发挥其免疫抑制作用。
